JAN 03, 2019 2:56 PM PST

The Endocannabinoid System and Why We Should Care

WRITTEN BY: Amy Loriaux

The nervous system, the cardiovascular system, the skeletal system, the endocrine system; these are all physiological systems that have probably made it into at least 7th-grade biology. We are very familiar with these systems and what they do: our nervous system is our brain and nerves; cardiovascular system pumps blood around the body; the skeletal system contains our bones and allows us to stand up; the endocrine system is responsible for our hormones, such as the stress hormone cortisol or the pancreatic hormone insulin. 

Source: Pixabay.com

Nevertheless, science keeps moving forward, and around the 1990s we discovered a new physiological system: the endocannabinoid system (ECS). What does the ECS do? It is probably best characterized as a "central regulatory system". What that really means is that it regulates physiological processes in the body to ensure that all systems are running in the optimal conditions - in other words, homeostasis. The ECS is made up of endocannabinoids (ECs) such as anandamide and 2-AG; EC receptors CB1, CB2, and a myriad of other proteins; the enzymes that create ECs; and the enzymes that destroy ECs. But where do these proteins come from, and how are they regulated?

Let us start where ECs are created. We will stick with anandamide since it was the first EC discovered. Anandamide is actually formed via two pathways, but its primary pathway is through the conversion of pre-existing AT-arachidonoyl phosphatidylethanolamine via the action of a type of enzyme called a phosphodiesterase. Okay, that was a lot of biochemistry. The interesting thing, though, is that anandamide (and other ECs) are made out of lipids. Most neurotransmitters are small molecules or larger neurohormones, but these are not lipid-based molecules. This is why THC and its metabolites can stay in your body for much longer than, say, cocaine. They can hang out in your fat cells.

The CB1 receptor is expressed abundantly in the nervous system and in various peripheral tissues. While the canonical view of neurotransmission is that receptors are on the post-synaptic side, CB1 is located on the pre-synaptic end and is thought to be used as a brake on neurotransmission. The CB2 receptor is expressed mainly in throughout the body. It is only slightly expressed in neurons. Instead, they are more widely expressed in microglia and the cardiovascular system. This receptor is mostly associated with the EC 2-AG, and it is action at this receptor that may mediate cannabidiol's non-psychoactive effects (e.g. pain reduction, anti-nausea, etc.). 

The ECS is an extremely complicated system and we have only touched the surface. The main thing to take away from this is that it is more than just a part of the central nervous system. It is its own system which serves a special function in the body, homeostasis. And not just of pH levels or metabolism (it does modulate metabolism) but stress levels, emotional states, sleep, and memory.

Source: Pixabay.com

Fun fact, ECs are thought to act as retrograde neurotransmitters because they go the "wrong way", or, "backward" across the synapse. They act as a "message received" communique from the post-synaptic cell. In certain memory regions in the brain, ECs may be responsible for "forgetting" stimuli that do not need to be remembered (the color of the office chair, the type of pants your colleague wore today, where did I put my keys?). Try to remember this if you decide to indulge (legally, please), that is, if you can.


Sources: PureRatios.com, Scientific American, LabRoots.com - Meet Anandamide - The "Bliss" Molecule, Wikipedia - 2-Arachidonoylglycerol, Science, Progress in Lipid Research, Biological Psychiatry, Journal of Biochemistry, TheRecoveryVilliage.com, British Journal of Pharmacology 

About the Author
Doctorate (PhD)
I currently work at a small CRO involved in clinical trial management.
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